This application requests the funds to purchase a new, digital electron microscope to replace one of the two 30-year-old, nearly-obsolete electron microscopes that constitute the unique "deep-etch" EM facility that operates at Washington University School of Medicine. This special form of electron microscopy has long been recognized as a uniquely valuable tool for biomedical research, and is a national resource that this institution wishes to promote and support long into the future. The deep-etch technique permits the visualization of all sorts of medically-relevant samples, from whole tissues down to individual cells and molecules, in all cases by quick-freeze and freeze-etch procedures that optimally preserve a lifelike state and avoid the artifacts inherent in most other forms of electron microscopy. It yields dramatic three- dimensional images of membranes and membrane topology that have provided critical insights into a wide range of biological problems, from how nerves communicate with each other, to how cancer cells migrate and invade tissues, to how viruses infect cells and replicate inside of them, to mention just a few topics. Deep-etch electron microscopy is thriving, and likely will be further developed and improved with time. However, the workhorse electron microscopes that are currently being used to do it are seriously out-of- date, and by being entirely film-based, have become serious bottlenecks in the process. With a modern electron microscope that includes a top-notch digital camera, the Deep-Etch EM Facility at Washington University School of Medicine will be able to greatly increase its output and streamline its operations, better train the next generation of electron microscopists, and support a wider range of research projects. Thus, this application is a request for a contemporary electron microscope to modernize an existing facility that is already of great value to Washington University and to all of medical science, but which is operating with antiquated equipment. [unreadable] [unreadable] [unreadable]